Mannose receptor-mediated gene transfer into macrophages using novel mannosylated cationic liposomes

被引：223

作者：

Kawakami, S ^{[1
]}

Sato, A ^{[1
]}

Nishikawa, M ^{[1
]}

Yamashita, F ^{[1
]}

Hashida, M ^{[1
]}

机构：

[1] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Drug Delivery Res, Sakyo Ku, Kyoto 6068501, Japan

来源：

GENE THERAPY | 2000年 / 7卷 / 04期

关键词：

gene delivery; cationic liposome; gene therapy; macrophages;

D O I：

10.1038/sj.gt.3301089

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A novel mannosylated cholesterol derivative, cholesten-5-yloxy-N-(4-((1-imino-2-beta-D-thiomannosyl-ethyl)amino)butyl) formamide (Man-C4-Chol), was synthesized in order to perform mannose receptor-mediated gene transfer with liposomes. Plasmid DNA encoding luciferase gene (pCMV-Luc) complexed with liposomes, consisting of a 6:4 mixture of Man-C4-Chol and dioleoylphosphatidylethanolamine (DOPE), showed higher transfection activity than that complexed with 3 beta [N-(N', N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol)/DOPE(6:4) and N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA)/DOPE(1:1) liposomes in mouse peritoneal macrophages. The presence of 20 mM mannose significantly inhibited the transfection efficiency of pCMV-Luc complexed with Man-C4-Chol/DC-Chol/DOPE(3:3:4) and Man-C4-Chol/DOPE(6:4) liposomes. High gene expression of pCMV-Luc was observed in the liver after intravenously injecting mice with Man-C4-Chol/DOPE(6:4) liposomes, whereas DC-Chol/DOPE(6:4) liposomes only showed marked expression in the lung. The gene expression with Man-C4-Chol/DOPE(6:4) liposome/DNA complexes in the liver was observed preferentially in the non-parenchymal cells and was significantly reduced by predosing with mannosylated bovine serum albumin. The gene expression in the liver was greater following intraportal injection. These results suggest that plasmid DNA complexed with mannosylated liposomes exhibits high transfection activity doe to recognition by mannose receptors both in vitro and in vivo.

引用

页码：292 / 299

页数：8

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